Kinetoplastids branched early from the eukaryotic lineage and include several parasitic protozoan species. Up to several hundred kinetoplastid genes are co-transcribed into polycistronic RNAs and individual mRNAs are resolved by coupled co-transcriptional trans-splicing of a universal splice-leader RNA (SL-RNA) and 3'-end maturation processes. Protein-coding genes lack RNA polymerase II promoters. Consequently, most of gene regulation in these organisms occurs post-transcriptionally. Over the last few years, many more genes that are regulated at the mRNA stability level and a few at the translation level have been reported. Almost all major trypanosome homologues of yeast/mammalian mRNA degradation enzymes have been functionally characterized and major pathways identified. Novel paradigms have also recently emerged: regulated post-transcriptional processing of cytoplasmic RNAs, SL-RNA transcriptional silencing-mediated global stress response, and Leishmania-specific large-scale modulation of post-transcriptional gene expression via inactive degenerated retroelements. Several of these developments have greatly benefited from the recently completed genomic sequences and functional genomic studies.